Organisms accumulate reactive oxygen species (hereinafter referred to as “ROS”) and reactive nitrogen species during their normal metabolic process and from external sources. ROS, including superoxide anion (O2), hydroxyl radical (OH), hydrogen peroxide (H2O2) and hypocholorous acid (HOCl), are involved in inflammation, cardiovascular diseases, cancers, aging-related diseases, metabolic diseases and atherosclerosis (Ames, B. N. et al., Proc. Natl. Acad. Sci. USA, 90:7915, 1993). ROS attack unsaturated fatty acids to cause the lipid peroxidation of the cell membrane, reduce the permeability of the membrane, reduce the activity of enzyme receptors, and cause damage to cell membrane proteins, thus causing cell inactivation (Dean, R. T. and Davies, M. J., Trends. Biochem. Sci., 18:437, 1993).
Organisms have natural defense mechanisms against the toxicity of ROS; nevertheless, the increase in the accumulation of ROS during the life of cells can cause irreversible oxidative damage to the cells (Tseng, T. H. et al., Food Chem. Toxicol., 35:1159, 1997). For this reason, antioxidants that eliminate free radical intermediates to delay or suppress oxidation processes have been requested. Although several potent synthetic antioxidants were already developed (Shimizu, K. et al., Lipids, 36:1321, 2001), these were shown to be highly potent carcinogens (Wichi, H. P. et al., Food Chem. Toxicol. 26:717-72, 1988). For this reason, the need to isolate antioxidants for use as health supplements from natural sources has been addressed. A wide range of natural substances, including phenolic compounds, nitrogen compounds and carotenoids, have antioxidant activity (Velioglu, Y. S. et al., J. Agric. Food Chem., 46:113, 1998).
Lichens are similar to non-flowering plants and are the symbiotic association of fungi (mycobionts) with algae and/or cyanobacteria (photobionts). The fungi in lichens form thalli or lichen substrates containing typical secondary metabolites (Ahmadjin, V. The lichen symbiosis. Wiley, New York, pp. 1-6, 1993). It is difficult to obtain sufficient amounts of natural lichen samples, and technology of cultivating large amounts of lichens is not known. For this reason, studies on lichens were insufficient compared to studies on higher plants. As the tissue culture method, mass-production method and biochemical analysis method for lichens have been improved, studies thereon have been actively conducted (Behera, B. C. et al., Lebensm. Wiss. Technol., 39:805, 2006). Compounds having various biological activities (including cytotoxicity, antifungal, antimicrobial, antioxidant and anti-inflammatory activities), including fatty acids, depsides, depsidones, dibenzofurans, diterpenes, anthraquinones, naphtoquinones, usninic acid, pulvinic acids, xanthones and epidithiopiperazinediones, were isolated from lichens (Müller, K., Appl. Microbiol. Biotechnol., 56:9-16, 2001). Lichens known to have antioxidant activity are mostly species of tropical and subtropical origin. Studies on the antioxidant activity of polar lichens are still insufficient (Bhattarai, H. D. et al., J. Nat. Med., 62:481, 2008).
Accordingly, the present inventors have made many efforts to isolate a novel compound having antioxidant activity from Antarctic lichens having various antioxidant activities and, as a result, have isolated the novel compound RAMALIN™ having very high antioxidant activity from the Antarctic lichen Ramalina terebrata having various antioxidant activities, thereby completing the present invention.